dbSNP rs850610: ATP1A1-AS1:n.345C>T (chr1-116406090-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000440951.1(ATP1A1):c.453-4045G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 212,480 control chromosomes in the GnomAD database, including 33,788 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.50 ( 22876 hom., cov: 31)

Exomes 𝑓: 0.57 ( 10912 hom. )

Consequence

ATP1A1
ENST00000440951.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.655

Variant links:

Genes affected

ATP1A1-AS1 (HGNC:28262): (ATP1A1 antisense RNA 1)

ATP1A1-AS1 links:

ATP1A1 (HGNC:799): (ATPase Na+/K+ transporting subunit alpha 1) The protein encoded by this gene belongs to the family of P-type cation transport ATPases, and to the subfamily of Na+/K+ -ATPases. Na+/K+ -ATPase is an integral membrane protein responsible for establishing and maintaining the electrochemical gradients of Na and K ions across the plasma membrane. These gradients are essential for osmoregulation, for sodium-coupled transport of a variety of organic and inorganic molecules, and for electrical excitability of nerve and muscle. This enzyme is composed of two subunits, a large catalytic subunit (alpha) and a smaller glycoprotein subunit (beta). The catalytic subunit of Na+/K+ -ATPase is encoded by multiple genes. This gene encodes an alpha 1 subunit. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

ATP1A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
ATP1A1-AS1	NR_024124.2 link	n.176C>T	non_coding_transcript_exon_variant	Exon 2 of 2
ATP1A1-AS1	NR_024125.2 link	n.452C>T	non_coding_transcript_exon_variant	Exon 3 of 3
ATP1A1-AS1	NR_024126.1 link	n.215C>T	non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
ATP1A1-AS1	ENST00000369491.2 link	n.345C>T	non_coding_transcript_exon_variant	Exon 4 of 4	1
ATP1A1-AS1	ENST00000369492.5 link	n.452C>T	non_coding_transcript_exon_variant	Exon 3 of 3	1
ATP1A1-AS1	ENST00000493908.2 link	n.178-4959C>T	intron_variant	Intron 1 of 2	1

Frequencies

GnomAD3 genomes

AF:

0.496

AC:

75350

AN:

151800

Hom.:

22875

Cov.:

show subpopulations

Gnomad AFR

AF:

0.148

Gnomad AMI

AF:

0.666

Gnomad AMR

AF:

0.513

Gnomad ASJ

AF:

0.568

Gnomad EAS

AF:

0.285

Gnomad SAS

AF:

0.726

Gnomad FIN

AF:

0.607

Gnomad MID

AF:

0.563

Gnomad NFE

AF:

0.680

Gnomad OTH

AF:

0.531

GnomAD4 exome

AF:

0.572

AC:

34612

AN:

60562

Hom.:

10912

Cov.:

AF XY:

0.580

AC XY:

17806

AN XY:

30706

show subpopulations

Gnomad4 AFR exome

AF:

0.118

Gnomad4 AMR exome

AF:

0.446

Gnomad4 ASJ exome

AF:

0.544

Gnomad4 EAS exome

AF:

0.255

Gnomad4 SAS exome

AF:

0.724

Gnomad4 FIN exome

AF:

0.616

Gnomad4 NFE exome

AF:

0.673

Gnomad4 OTH exome

AF:

0.578

GnomAD4 genome

AF:

0.496

AC:

75354

AN:

151918

Hom.:

22876

Cov.:

AF XY:

0.495

AC XY:

36728

AN XY:

74240

show subpopulations

Gnomad4 AFR

AF:

0.147

Gnomad4 AMR

AF:

0.513

Gnomad4 ASJ

AF:

0.568

Gnomad4 EAS

AF:

0.286

Gnomad4 SAS

AF:

0.726

Gnomad4 FIN

AF:

0.607

Gnomad4 NFE

AF:

0.680

Gnomad4 OTH

AF:

0.532

Alfa

AF:

0.636

Hom.:

46784

Bravo

AF:

0.463

Asia WGS

AF:

0.469

AC:

1632

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.4

DANN

Benign

0.78

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over